首页> 中文期刊> 《细胞与分子免疫学:英文版》 >High levels of circulating GM-CSF^(+) CD4^(+) T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study

High levels of circulating GM-CSF^(+) CD4^(+) T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study

         

摘要

Granulocyte colony-stimulating factor(GM-CSF),produced by CD4^(+)T cells,has recently been implicated in the pathogenesis of inflammatory diseases,such as multiple sclerosis and juvenile arthritis.However,the role of GM-CSF-producing CD4^(+)T cells in sepsis remains unknown.This study reports peripheral changes in GM-CSF-producing CD4^(+)T cells in septic patients and the possible underlying mechanism by which GM-CSF influences the outcome of sepsis.Forty-three septic patients,20 SIRS patients,and 20 healthy controls were enrolled in this study and followed for 28 days to assess mortality.We measured the peripheral frequency of GM-CSF^(+)CD4^(+)T cells and recorded their associated relationship with disease progression.Our data demonstrated that peripheral GM-CSF-producing CD4^(+)T cells were significantly higher in septic patients than in both SIRS patients and healthy controls.These cells exhibit a memory phenotype and impaired IFN-γ-secreting capacity in sepsis patients.Using a receiver operating curve analysis with 8.01%as a cut-off point,the percentage of GM-CSF^(+)CD4^(+)T cells could predict the outcome of septic patients.Combined with the increase in GM-CSF-producing CD4^(+)T cells,inflammatory cytokines IL-1βand IL-6 were also upregulated.Using an in vitro neutrophil model,we found that GM-CSF inhibited C3aR expression,while inducing IL-8 production.Furthermore,this effect was transferrable in plasma from sepsis patients and was attenuated by inhibition of GM-CSF using an anti-GM-CSF antibody.These results indicate that GM-CSF-producing CD4^(+)T cells may serve as a marker of sepsis severity.Thus,targeting GM-CSF overproduction may benefit sepsis patients.

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